In vivo imaging of the surface of the nervous system and its fluid cavities has long been a goal of neuroradiologists. In many cases this requires contrast enhancement of the cerebrospinal fluid spaces (CSF). Unfortunately, no practical and safe contrast agents were available in the past. Recent advances in the development of water-soluble contrast agents now allow direct delineation of the brain surfaces and its cavities. However, even the newest and most benign radiographic contrast agents produce neurotoxic effects when applied directly to the central nervous system (CNS). In order to avert the toxic effects of contrast agents, it would be helpful to understand the etiology of these adverse effects. One of the major clinical sequelae of applying contrast agents directly to the CNS is seizures. There is little information as to how these drugs induce seizures. This research will approach that problem using two methodologies. First, the intracebular effects of these drugs will be investigated by use of the in vitgro guinea-pig hippocampal slice. Intracellular recordings from these neurons, after exposure to different contrast agents, will be used to identify and confirm specific neurophysiological effects of these drugs. From these studies, mechanisms of action will be proposed. Second, the cat lumbar spinal cord will be used to confirm the in vitro results in an in vivo preparation. The spinal cord preparation will also be used to test the effects of intravascular contrast injection. Using these techniques, the mechanism of the neurotoxic effects, reflected as altered CNS electrical activity will be better understood. From this information, modifications of the chemistry of these compounds or diminution of their toxic effects by combination with other drugs will be proposed.